Efficient and scalable expansion of human pluripotent stem cells under clinically compliant settings: a view in 2013.

Human pluripotent stem cells (hPSCs) hold great promise for revolutionizing regenerative medicine for their potential applications in disease modeling, drug discovery, and cellular therapy. Many their applications require robust and scalable expansion of hPSCs, even under settings compliant to good clinical practices. Rapid evolution of media and substrates provided safer and more defined culture conditions for long-term expansion of undifferentiated hPSCs in either adhesion or suspension. With well-designed automatic systems or fully controlled bioreactors, production of a clinically relevant quantity of hPSCs could be achieved in the near future. The goal is to find a scalable, xeno-free, chemically defined, and economic culture system for clinical-grade expansion of hPSCs that complies the requirements of current good manufacturing practices. This review provides an updated overview of the current development and challenges on the way to accomplish this goal, including discussions on basic principles for bioprocess design, serum-free media, extracellular matric or synthesized substrate, microcarrier- or cell aggregate-based suspension culture, and scalability and practicality of equipment.